Indicators of a pro-tumor immune response are evident at early stages of breast cancer.

With advances in checkpoint inhibitor and CAR T-cell therapies, among other advances in immunotherapy, this is an exciting time to be a tumor immunologist. We are witnessing the transition of decades of work at the bench leading to substantial success in the clinic. While work continues developing new and improving existing immunotherapies, there remains a great deal of basic tumor immunology still to learn, information that can only lead to greater success in the clinic. One area in need of more attention is understanding the immune response at early stages of breast cancer. While there is no question that early diagnosis and treatment save lives, a greater understanding about the immune response during early stages of breast cancer may reveal information that could assist in monitoring individuals at risk of breast cancer, and could have implications for patients diagnosed at early stages of disease, and may provide important information about the origins of an immune-suppressive environment. Here, we review studies that have looked at the very early immune response to breast cancer focusing on patients with DCIS, before invasion in spontaneous transgenic murine mammary carcinoma models, and before transplantable or orthotopic murine mammary carcinoma models become palpable. The findings revealed that indicators of a pro-tumor immune response are already present at early stages of disease.

[Assessment of the cytokine-producing resource of tumor biopsy samples from patients with invasive carcinoma of no special type and with non-malignant breast diseases]. / Otsenka tsitokinprodutsiruiushchego resursa bioptatov opukholei patsientov s invazivnoi kartsinomoi nespetsificheskogo tipa i s nezlokachestvennymi zabolevaniiami molochnoi zhelezy.

Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1ß and the ratio of IL1ß/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1ß, as well as the ratio of IL1ß/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.

The microbiome and breast cancer: a review.

The human microbiome plays an integral role in physiology, with most microbes considered benign or beneficial. However, some microbes are known to be detrimental to human health, including organisms linked to cancers and other diseases characterized by aberrant inflammation. Dysbiosis, a state of microbial imbalance with harmful bacteria species outcompeting benign bacteria, can lead to maladies including cancer. The microbial composition varies across body sites, with the gut, urogenital, and skin microbiomes particularly well characterized. However, the microbiome associated with normal breast tissue and breast diseases is poorly understood. Collectively, studies have shown that breast tissue has a distinct microbiome with particular species enriched in the breast tissue itself, as well as the nipple aspirate and gut bacteria of women with breast cancer. More importantly, the breast and associated microbiomes may modulate therapeutic response and serve as potential biomarkers for diagnosing and staging breast cancer.

Rosai-Dorfman Disease of the Breast With Variable IgG4+ Plasma Cells: A Diagnostic Mimicker of Other Malignant and Reactive Entities.

Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (<1/50 HPF) to numerous (>50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.

Systemic vasculitis involving the breast: a case report and literature review.

Systemic vasculitis involving the breast is a rare clinical condition and may mimic breast cancer or mastitis clinically or radiographically. Here, we report a case of polyarteritis nodosa (PAN) with breast involvement and perform a literature review of published cases of systemic vasculitis affecting the breast to better understand this disorder. We report a case of PAN affecting the right breast in a young woman. A retrospective review was performed by searching Medline, Embase, Web of Science, the Cochrane Library, and Scopus for cases of systemic vasculitis involving the breast written in English up to June 1st, 2018. A 27-year-old woman presented with a painful mass in the right breast was diagnosed as PAN by the biopsy. She was treated with prednisone and methotrexate for 6 months, at which time her condition had stabilized and inflammatory markers had normalized. A total of 66 cases were identified, with granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), and PAN as the main types. The typical manifestation was mass (79.2%, 53/67) in the breast, and all diagnoses were made by the pathology of the breast biopsy. Glucocorticoid and immunosuppressant were the main therapies, and 74.6% (50/67) patients achieved remission during follow-up. Our case and a literature review of 66 cases of systemic vasculitis involving the breast reveal the importance of tissue biopsy to obtain a definitive diagnosis, because the vasculitis subtype strongly influences prognosis.

Lymphocyte subsets contribute to the degree of lobulitis and ductitis in sclerosing lymphocytic lobulitis of the breast.

AIMS: Sclerosing lymphocytic lobulitis (SLL) of the breast is characterised by lymphocytic lobulitis, ductitis, vasculitis and dense keloidal fibrosis with epithelioid fibroblasts. However, the subsets of the infiltrating lymphocytes and their contribution to disease progression have not been fully explored. METHODS: CD20, CD3, CD4, CD8 and regulatory T (Treg) lymphocytes were evaluated in the epithelial and vascular areas in SLL. The relationship between the lymphocyte subset in different regions and the degree of inflammation was analysed. RESULTS: Lymphocytic infiltration was mainly located in peri-lobular, peri-ductal and peri-vascular areas. No significant differences between CD20 and CD3 lymphocytes were found in peri-epithelial areas. However, there were more intra-ductal/lobular epithelial CD3 than CD20 lymphocytes (p<0.001). For T lymphocyte subsets, more CD4 than CD8 lymphocytes were found in the peri-lobular/vascular regions (p≤0.026); but an opposite trend was seen in the intra-ductal/lobular regions (p<0.001). In the peri-lobular/vascular regions, generally, different lymphocyte subsets correlated with each other. Interestingly, in the peri-ductal region, only CD4 lymphocytes showed significant correlations with all other subsets (p≤0.020). Regarding their relationship with the degree of inflammation, significant positive correlations were observed for all subsets in peri-vascular/lobular regions (p≤0.045). Only regulatory T cells, but not the others, at the peri-ductal region showed significant correlation with the degree of inflammation at all three regions (p≤0.014). CONCLUSIONS: In addition to B lymphocyte subsets, T lymphocyte subsets could be involved differently in SLL. CD4 lymphocytes may have a pivotal role in recruiting other subsets to the inflamed site, and triggered the cascade of inflammatory changes resulting in fibrosis.

Evaluating breast lymphoplasmacytic infiltrates: a multiparameter immunohistochemical study, including assessment of IgG4.

Lymphoplasmacytic infiltrates in the breast, a modified skin appendage, include lymphocytic lobulitis, other nonspecific benign proliferations, and mucosa-associated lymphoid tissue (MALT)-type lymphoma. Distinguishing these entities, all of which may be B-cell rich and may have associated sclerosis, can be difficult. In addition, the proportion that represents IgG4-related disease is unknown, and the similarity of MALT lymphomas to primary cutaneous marginal zone lymphoma is uncertain. To address these questions, the clinical, histologic, and immunohistochemical features of 50 benign and malignant breast lymphoplasmacytic infiltrates (10 lymphocytic lobulitis, 1 granulomatous, 19 not otherwise specified, 20 MALT lymphomas) were evaluated. Compared with the MALT lymphomas, benign cases had a less dense infiltrate (P < .001), fewer but more histologically apparent germinal centers (P < .001), and more marked fibrosis (P < .0001). Greater than 60% B cells were present in 23% (7/30) benign cases versus 75% (15/20) MALT lymphomas (P = .0003). Plasma cells were predominantly IgG+ in 83% (24/29) benign cases and predominantly IgM+ in 73% (14/19) MALT lymphomas (P < .0001). None of the benign cases had greater than 50 IgG4+ plasma cells/high-power field, and only 1 lymphocytic lobulitis case had an IgG4/IgG ratio exceeding 40% and no clinical evidence for extramammary IgG4-related disease. Although there may be some overlapping features, routine histopathology together with limited immunohistochemical stains can distinguish benign from neoplastic lymphoplasmacytic infiltrates in the breast. Despite frequent sclerosis, the breast is not a common site of unrecognized IgG4-related sclerosing disease. Although there are similarities, breast MALT lymphomas can be separated from cutaneous marginal zone lymphoma.

Immune cell-mediated protection of the mammary gland and the infant during breastfeeding.

Breastfeeding has been regarded first and foremost as a means of nutrition for infants, providing essential components for their unique growth and developmental requirements. However, breast milk is also rich in immunologic factors, highlighting its importance as a mediator of protection. In accordance with its evolutionary origin, the mammary gland offers via the breastfeeding route continuation of the maternal to infant immunologic support established in utero. At birth, the infant's immune system is immature, and although it was exposed to the maternal microbial flora during pregnancy, it experiences an abrupt change in its microbial environment during and after birth, which is challenging and renders the infant highly susceptible to infection. Active and passive immunity protects the infant via breast milk, which is rich in immunoglobulins, lactoferrin, lysozyme, cytokines, and numerous other immunologic factors, including maternal leukocytes. Breast milk leukocytes provide active immunity and promote development of immunocompetence in the infant. Additionally, it has been speculated that they play a role in the protection of the mammary gland from infection. Leukocytes are thought to exert these functions via phagocytosis, secretion of antimicrobial factors and/or antigen presentation in both the mammary gland and the gastrointestinal tract of the infant, and also in other infant tissues, where they are transported via the systemic circulation. Recently, it has been demonstrated that breast milk leukocytes respond dynamically to maternal as well as infant infections, and are fewer in nonexclusively compared with exclusively breastfeeding dyads, further emphasizing their importance for both the mother and infant. This review summarizes the current knowledge of human milk leukocytes and factors influencing them, and presents recent novel findings supporting their potential as a diagnostic marker for infections of the lactating breast and of the breastfed infant.

Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis.

BACKGROUND: The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. METHODS: We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. RESULTS: Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. CONCLUSIONS: The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not epiphenomena, but likely reflect an antigen-driven autoimmune response triggered by epitopes developing in the mammary gland during breast carcinogenesis. Our results support the validity of the multiple studies reporting association of autoantibodies with breast cancer. Results further suggest significant promise for the development of panels of breast cancer-specific, premalignant-phase autoantibodies, as well as studies on the autoantibody response to tumor associated antigens in the pathogenesis of cancer.

Erdheim-Chester disease involving the breast--a rare but important differential diagnosis.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by multisystem infiltration by foamy histiocytes surrounded by fibrosis. ECD often involves the long bones, skin, and retroperitoneum, whereas breast involvement is very rare with only 6 reported cases in English literature. We report a case of ECD presenting within the right breast as a clinically malignant tumor, in addition to bilateral sclerotic lesions of the femurs, bilateral soft tissue masses of the cerebellum, and multiple subcutaneous nodules on the abdominal wall in a 61-year-old woman. Histologically, there was a prominent infiltrate of foamy histiocytes with scattered Touton-type giant cells, lymphocytes, and plasma cells. The foamy histiocytes were arranged in small clusters or scattered singly in the background of fibrosis. However, in some areas, there was a prominent proliferation of fibrosis with scant cellular infiltrate including histiocytes. The diagnosis of ECD was made by characteristic histopathologic features in addition to clinical-radiographic features and the typical immunoprofile (positive for cluster of differentiation 68 [CD68], CD163, and p16; negative for CD1a and S-100). Although rare, ECD must be considered in the differential diagnosis of clinically malignant tumor of the breast. To our knowledge, this is the second case of ECD involving the breast in which a valine 600 glutamic acid mutation was detected, which probably represents a clonal disorder of non-Langerhans cells.

[Immunologic predictors of diabetes mellitus in menopausal breast cancer patients].

Although the relations between diabetes mellitus (DM) and breast cancer (BC) are lately widely discussed, the actual causes for cancer predisposition in patients with diabetes are currently unclear. This study was designed to define the frequency of DM immunological predictors occurrence and immune system function shifts in patients with breast cancer. Sixty four BC patients, 19 patients with benign breast conditions and 40 healthy individuals were included. The lymphocyte sensibilization with insulin suppressed by prostaglandin-synthesizing cells or cells with histamine receptor expression (DM predictor) is more common in BC patients than in control group (29 of 56 vs 5 of 37, p < 0.001). This is not a tumor marker, but rather is an objective factor reflecting higher occurrence of insulin resistance in this group. For BC patients is also characteristic the lower PHA-stimulated peripheral lymphocyte proliferation rate probably caused by increase in short-lived suppressor cell activity, a usual sign of the impairment of cell-mediated immunity. It is also possible, that the immunologic predictors of DM associated with insulin resistance, combined with the effects of short-lived suppressor cells, promote tumor cell proliferation.

Inflammatory breast diseases during lactation: health effects on the newborn-a literature review.

Breastfeeding-associated inflammatory breast diseases appear especially during the first twelve weeks postpartum and are the most common reason for early cessation of breastfeeding. It also becomes increasingly evident that these inflammatory mammary diseases are triggered or perpetuated in a large part by psychosocial stress. Immunological processes taking place during this cascade in the mammary gland and consequences for the breastfeed newborn are mostly yet unknown. This review summarizes insights from studies on modulation of cytokine levels in breast milk during inflammatory processes like milk stasis and mastitis systematically. It also gives an overview on possible pathological effects, which these cytokine changes in the breast milk might have on the newborn.

Diffuse dermal angiomatosis: A previously undescribed pattern of immunoglobulin and complement deposits in two cases.

Two cases of diffuse dermal angiomatosis are reported in middle-aged women. This rare disease of unknown origin is characterized by increased dermal angiomatosis and ulceration. The clinical and histologic presentations of the presently reported lesions were typical for this disorder. Endothelial cells exhibited a normal immunophenotype. The perivascular basement membranes showed a distribution of collagen alpha chains typical for blood vessels, but not for lymphatics. Immunohistochemistry revealed other undescribed features. At the site of the clinical lesions, linear and granular deposits of immunoglobulins A and M, and complement were found around the vessels and at the dermal-epidermal junction. The same deposits were also found restricted to the dermal-epidermal junction in the peripheral clinically intact skin. No serological signs of auto-immune disorder were detected in one patient. A monoclonal gammopathy was disclosed in the other patient. A pattern of immunoreactant deposits similar to that disclosed in the two patients was not found in the control specimens, and has not been described so far in other types of vascular hyperplasia and neoplasia. A pathogenic role of these deposits is unsettled and should be further explored.

Thyroid autoimmunity in patients with malignant and benign breast diseases before surgery.

BACKGROUND: Previous studies have demonstrated a high prevalence of thyroperoxidase antibodies (TPOAb) and autoimmune hypothyroidism in breast cancer (BC). These studies have been performed in BC patients generally 20-30 days after mastectomy. It is known that stress may have an influence on the immune system and a relation between stressful events and the onset or worsening of autoimmune thyroid disorders has been reported by several authors. The aim of the study was to evaluate the prevalence of autoimmune thyroid disease in patients with nodular breast disease selected for surgery before any treatment. Our hypothesis was that the high prevalence of thyroid autoimmune disorders in BC is independent of stressful events represented by surgery and/or anaesthetic procedures. METHODS: Our series included 61 consecutive women aged 52.8 +/- 10.2 yrs (mean age +/- s.d.) with nodular breast disease selected for breast surgery: 36 out of 61 of them (59%) had BC and 25 out of 61 had benign breast disease (BBD). Controls included 100 healthy age-matched women. All patients and control subjects were submitted to clinical, ultrasound thyroid evaluation and serum-free thyroxine (FT4), serum-free tri-iodothyronine (FT3), TSH, TPOAb and thyroglobulin antibodies (TgAb) determination. RESULTS: Mean FT3, FT4 and TSH concentration showed no differences between BC patients, BBD patients and controls. The prevalence of TPOAb in BC patients (12/36: 33.33%) was significantly higher than in BBD patients (5/25: 20%) (P < 0.01) and in controls (8/100: 8%) (P < 0.01). Similarly, the prevalence of TgAb in BC patients was 12 out of 36 (33.33%) significantly higher than that detected in BBD patients (4/25: 16%) (P < 0.01) and in controls (12/100: 12%) (P < 0.01). Of the 36 BC patients, 20 showed a diffuse hypoechogenicity of the thyroid gland to ultrasound evaluation, significantly higher than in BBD (7/25: 28%) (P = 0.03). Of the 20 BC patients who showed a hypoechogenic pattern of thyroid gland, 10 (50%) were associated with antithyroid antibodies positivity (TAb). This finding was present in two of seven BBD (28.57%) (P < 0.0001). Only two controls showed focal hypoechogenicity of the thyroid gland. Generally, 24 out of 36 (66.7%) of BC and 9 out of 25 (36%) of BBD (P = 0.02) had signs of thyroid autoimmunity consistent with the hypoechogenic pattern of thyroid gland associated or not with TAb; 2 out of 36 (5.55%) of BC and 1 out of 25 (4%) of BBD patients had autoimmune hypothyroidism and no hypothyroidism was found in controls. CONCLUSIONS: The results of this study confirm the strong relation between thyroid autoimmunity and BC. This finding is independent of stressful events represented by surgery or anaesthetic procedures. The present data call attention to the usefulness of screening for autoimmune thyroid disorders in patients with nodular breast disease selected for surgery.

Prevalence of bacteria in the nipple discharge of patients with duct ectasia.

The aim of this study was to identify the aerobic and the anaerobic microorganisms which can be related to duct ectasia. The patients were divided into two groups. Group 1 comprised 100 patients with coloured nipple discharge (duct ectasia group), and Group 2 (the control group) was composed of 50 patients without nipple discharge. The culture media used were BHI-PRAS, blood agar, mannitol agar and MacConkey agar. There was a high frequency of bacterial growth in the two groups: 85% in Group 1 and 88% in Group 2. The most prevalent bacteria were Staphylococcus aureus and Staphylococcus epidermidis. There was a statistically significant higher rate of smokers in the duct ectasia group compared with the control group, 25 (25%) patients vs. 5 (10%), respectively (p = 0.03). These findings allow us to put forth the hypothesis that the genesis of duct ectasia may be a non-infectious inflammatory process.

Breast inflammatory gigantomastia in a context of immune-mediated diseases.

CONTEXT: Localized breast lesions have been described in lupic or diabetic patients. However, the description of breast gigantomastia in women presenting with autoimmune diseases has not been reported. SETTING: The study took place within the Department of Endocrinology and Reproductive Medicine, Necker Hospital, Paris, France. PATIENTS: We describe eight patients with inflammatory gigantomastia, occurring in a context of immune-mediated diseases: myasthenia, chronic arthritis, or thyroiditis. MAIN OUTCOME MEASURES: Together with hormonal, immunological, and breast magnetic resonance imaging (MRI) evaluation, breast histology enabled us to perform immunocytochemical and indirect immunofluorescence studies. Control sera were obtained from patients with (n = 10) and without (n = 7) antinuclear antibodies. RESULTS: Six of the eight patients developed gigantomastia either at puberty or during pregnancy. Neither a hormonal oversecretion nor a specific immunological pattern was observed. All patients except one presented antinuclear antibodies. Histological study revealed a diffuse, stromal hyperplasia and a severe atrophy of the lobules. A rarefaction of adipocytes was also noted, as previously suggested on MRI. There was a perilobular lymphocytic infiltrate made of CD3+ lymphocytes. Study of sera from five of six cases of gigantomastia showed a nuclear immunofluorescence pattern in normal mammary ductal and lobular glandular epithelium, as well as in kidney and intestine epithelial cells. In control sera, a nuclear signal was observed only when antinuclear antibodies were present. CONCLUSIONS: We suggest that breast tissue may be a target tissue in autoimmune diseases, this process being favored by the hormonal milieu. However, the precise mechanism of such association is not individualized. The fact that stromal hyperplasia is the main histological feature justifies the search for the involvement of growth factors in such a process.

Radiologic evaluation of uncommon inflammatory and reactive breast disorders.

The radiologic features of breast lesions caused by immunologic, reactive, and noncurrent infectious diseases often mimic those of malignancy, frequently constituting a diagnostic challenge even if the underlying disease is known. Churg-Strauss syndrome mimics carcinomatous mastitis. Amyloidosis usually manifests as a suspicious mass, often accompanied by microcalcifications. Wegener granulomatosis and sarcoidosis often manifest as irregular masses, although sarcoidosis can also manifest as round, well-defined masses reflecting intramammary node involvement. Diabetic mastopathy is a rare but well-known entity in patients with long-standing insulin-dependent diabetes. Breast involvement by necrobiotic xanthogranulomatosis is rare and manifests as multiple bilateral asymmetric lesions. Multiple clustered hypoechoic tubular structures in a large hypoechoic mass seen after pregnancy can be suggestive of granulomatous mastitis. Mammary tuberculosis can manifest with a nodular, diffuse, or sclerosing pattern. A granulomatous inflammatory reaction must be carefully evaluated because it constitutes the major feature of a diverse group of diseases that includes vasculitis, granulomatous mastitis, tuberculosis, and carcinoma-associated sarcoidlike reactions. Core biopsy can play a major role in developing a differential diagnosis for these rare immunologic, inflammatory, or infectious disorders affecting the breast, and knowledge of these entities can, in the appropriate clinical setting, help the radiologist narrow the differential diagnosis, although cancer must be excluded definitively.